7-90984204-T-G

Variant names:

• chr7-90984204-T-G
• rs766082964
• NM_001287135.2:c.1004T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001287135.2(CDK14):​c.1004T>G​(p.Met335Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,538 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M335I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDK14 NM_001287135.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46
• Publications: 0 publications found

Genes affected

CDK14 (HGNC:8883): (cyclin dependent kinase 14) Enables cyclin binding activity and cyclin-dependent protein serine/threonine kinase activity. Involved in G2/M transition of mitotic cell cycle and regulation of canonical Wnt signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Part of cytoplasmic cyclin-dependent protein kinase holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.1004T>G	p.Met335Arg	missense_variant	Exon 10 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.950T>G	p.Met317Arg	missense_variant	Exon 9 of 14		NP_036527.1
CDK14	NM_001287136.1	c.866T>G	p.Met289Arg	missense_variant	Exon 9 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.617T>G	p.Met206Arg	missense_variant	Exon 8 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.1004T>G	p.Met335Arg	missense_variant	Exon 10 of 15	1	NM_001287135.2	ENSP00000369390.3
CDK14	ENST00000265741.7	c.950T>G	p.Met317Arg	missense_variant	Exon 9 of 14	1		ENSP00000265741.3
CDK14	ENST00000406263.5	c.866T>G	p.Met289Arg	missense_variant	Exon 9 of 14	1		ENSP00000385034.1
CDK14	ENST00000436577.3	c.617T>G	p.Met206Arg	missense_variant	Exon 8 of 13	2		ENSP00000398936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460538 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726714

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110846

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.092	T;.;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.17	N;.;.;.
PhyloP100		7.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.51
Sift	Benign	0.040	D;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.93	P;P;.;P
Vest4		0.78
MutPred		0.34		Gain of methylation at K336 (P = 0.0222);.;.;.;
MVP		0.64
MPC		0.72
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.75
gMVP		0.93
Mutation Taster		=6/94	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766082964; hg19: chr7-90613519;